The increasing interest in developing tools to predict drug absorption through mucosal surfaces is fostering the establishment of epithelial cell-based models. Cell-based in vitro techniques for drug ... [more ▼]

The increasing interest in developing tools to predict drug absorption through mucosal surfaces is fostering the establishment of epithelial cell-based models. Cell-based in vitro techniques for drug permeability assessment are less laborious, cheaper and address the concerns of using laboratory animals. Simultaneously, in vitro barrier models that thoroughly simulate human epithelia or mucosae may provide useful data to speed up the entrance of new drugs and new drug products into the clinics. Nevertheless, standard cell-based in vitro models that intend to reproduce epithelial surfaces often discard the role of mucus in influencing drug permeation/absorption. Biomimetic models of mucosae in which mucus production has been considered may not be able to fully reproduce the amount and architecture of mucus, resulting in biased characterization of permeability/absorption. In these cases, artificial mucus may be used to supplement cell-based models but still proper identification and quantification are required. In this review, considerations regarding the relevance of mucus in the development of cell-based epithelial and mucosal models mimicking the gastro-intestinal tract, the cervico-vaginal tract and the respiratory tract, and the impact of mucus on the permeability mechanisms are addressed. From simple epithelial monolayers to more complexes 3D structures, the impact of the presence of mucus for the extrapolation to the in vivo scenario is critically analyzed. Finally, an overview is provided on several techniques and methods to characterize the mucus layer over cell-based barriers, in order to intimately reproduce human mucosal layer and thereby, improve in vitro/in vivo correlation. [less ▲]

The development of cell based advanced therapeutic medicinal products (ATMPs) for bone repair has been expected to revolutionize the health care system for the clinical treatment of bone defects. Despite ... [more ▼]

The development of cell based advanced therapeutic medicinal products (ATMPs) for bone repair has been expected to revolutionize the health care system for the clinical treatment of bone defects. Despite this great promise, the clinical outcomes of the few cell based ATMPs that have been translated into clinical treatments have been far from impressive. In part, the clinical outcomes have been hampered because of the simplicity of the first wave of products. In response the field has set-out and amassed a plethora of complexities to alleviate the simplicity induced limitations. Many of these potential second wave products have remained "stuck" in the development pipeline. This is due to a number of reasons including the lack of a regulatory framework that has been evolving in the last years and the shortage of enabling technologies for industrial manufacturing to deal with these novel complexities. In this review, we reflect on the current ATMPs and give special attention to novel approaches that are able to provide complexity to ATMPs in a straightforward manner. Moreover, we discuss the potential tools able to produce or predict 'goldilocks' ATMPs, which are neither too simple nor too complex. [less ▲]

Advanced drug delivery systems rely on the availability of biocompatible materials. Moreover, biodegradability is highly desirable in the design of those systems. Consequently, aliphatic polyesters appear as a class of promising materials since they combine both properties. Nevertheless, their use in practical biomedical systems relies on clinical approval which not only depends on the material itself but also on its reproducible synthesis with the absence of residual toxics. The first sections of this review aim at reporting on the evolution of the initiators/catalytic systems and of the synthesis conditions (particularly the use of supercritical CO2 as polymerization medium) in order to produce aliphatic polyesters with controlled macromolecular parameters by still "greener" ways. In addition, the further development of delivery systems also depends on the synthesis of materials exhibiting novel properties, such as amphiphilicity or pH-sensitivity that are emerging from the active research in macromolecular engineering. Functionalizing aliphatic polyesters is quite tedious due to their sensitivity towards hydrolytic degradation. The last section of this review is discussing several strategies to obtain functional (co)polyesters of various architectures providing them with novel properties. [less ▲]

Functional imaging techniques provide complimentary information to that provided by structural studies such as MRI and CT. Functional imaging is based upon known parameters such as physiology, metabolism ... [more ▼]

Functional imaging techniques provide complimentary information to that provided by structural studies such as MRI and CT. Functional imaging is based upon known parameters such as physiology, metabolism, biochemistry, pharmacology, and any other biological process. As such, this methodology plays a major role in understanding the basic mechanisms of a multitude of disorders, accurate diagnosis of certain diseases, and developing effective treatment for serious illnesses such as cancer and central nervous system maladies. Although this type of imaging can be performed with various modalities, nuclear procedures have played the leading role in this discipline. Advances made in labeling various radionuclides to biologically important compounds, and development of sophisticated instruments have substantially contributed to the growth of the field of functional imaging. The introduction of positron emission topography (PET), which is based on imaging of compounds labeled with elements such as carbon, nitrogen, and fluorine, has added a major dimension to the evolution of the discipline. This review deals with a brief introduction to the methodologies utilized with radiolabeled tracers and then deals with specific applications of this technology. These applications include assessment of blood flow and metabolism, receptor imaging, elucidating the pathophysiologic process, evaluating role of labeled therapeutic agents, and the potential of these techniques in the development of novel biologic therapies. Functional imaging with radiolabeled tracers will play an increasingly important role in modern medicine, and its impact will be substantial in the management of patients with various disorders. [less ▲]